Pulmonary alveolar proteinosis (PAP) is a recently recognized disease of unknown etiology affecting primarily lungs with characteristic deposition of a PAS-positive proteinaceous material in the alveoli. No specific therapy nor specific preventive measures are available. Review of the literature, as well as our own experience with patients with PAP, indicate that this disease is most likely caused by some postnatal factor, i.e. infection or defective host response to some exogenous substance. This idea is derived from three pieces of evidence: 1) About 1/3 of 23 children with PAP were reported to have "thymic alymphoplasia", a condition in which there is clearly defective immune function. 2) About 10 percent of reported cases of PAP succumbed to infection by unusual pathogenic organisms such as norcardia, aspergillus. 3) A surprising paucity of cellular reaction at the site of lung lesion, despite massive accumulation of pathologic fluid in the alveolar space. Furthermore, inhalation of quartz dust, silica dust, or ingestion of iprindole by experimental animals (especially rats) have been reported to produce either silicosis or pulmonary lesions similar to PAP in man, depending on the immunologic preconditioning of the animal. We propose to search for a defective host response using modern immunologic methodology. We will attack the question by three approaches: 1) Cellular immune responses, 2) Phagocytic and inflammatory response, 3) Humoral antibody response in the serum, as well as in the bronchoalveolar lavage fluid. Our long term goal is to discover means of specific therapy and prevention of PAP.